Circulating blood contains a diverse set of cellular and molecular elements that can be detected and quantified to indicate the presence of cancers, allergies, heart disease, and neurodegenerative disease. The detection of bloodborne biomarkers has value not only for disease detection, but also for informing the prescription choice for personalized therapies and in the monitoring of these treatments. For example, biomarker levels can help assist the development of novel molecular-targeted therapeutic strategies, identify patients who are likely to benefit from a specific targeted treatment, as well as provide molecular endpoints to predict and monitor treatment efficacy.
In the most general sense, a biomarker is any measurable factor that differentiates a normal biological process from a disease-related process or its response to therapy. In the search for cancer biomarkers, the quantitative analysis of products of cancer cells, the tumor microenvironment, the host's response, and the interaction between these three components has yielded several potential candidates. Circulating protein markers are currently in clinical use for the diagnoses of ovarian, pancreatic, colon, and prostate cancers. Exosomal microRNAs (miRNA), which are 18-24 bases long double stranded noncoding RNA that regulate expression through control over mRNA and protein translation, is another class of biomarker molecules that has been keenly studied as their expression is altered in disease states, notably in cancers. A special consideration for detecting cancer biomarkers is that tumors initially develop from a small population of defective cells, and hence it is highly desirable to be able to detect the presence of the smallest number of tumor cells (i.e. early intervention) when a patient's clinical outcomes and prognosis are still favorable. Although reports of several bioanalytical techniques for cancer biomarker detection exist, an unmet, critical limitation is the reliable and accurate detection of cancer biomarkers mainly due to (a) insufficient sensitivity of the assay and (b) insufficient dynamic range needed to detect biomarkers anywhere from the low ng/mL to the low pg/mL range.
To maximize the applicability and accessibility of a biomarker detection platform, the ability to perform sensing noninvasively is highly desirable, particularly if it can utilize a sample comprised of a single droplet of blood. The adoption of biomarker tests may be accelerated by methods that can be performed with minimal sample preparation and technical expertise, potentially enabling testing to be performed in close proximity to the patient. Such a portable platform would help reduce costs, minimize sample degradation, provide on-spot diagnosis thus alleviating patient stress, and finally guide the course therapy especially when timely adjustments in treatment are critical. It is further desirable for detection instruments used in a point-of-care setting to be inexpensive, compact, and rugged.